AUTHOR=Xue Yu-juan , Wang Yu , Zhang Le-ping , Lu Ai-dong , Jia Yue-ping , Zuo Ying-xi , Zeng Hui-min 

TITLE=Prognostic significance of Wilms’ tumor gene 1 expression in children with B-cell precursor acute lymphoblastic leukemia

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1297870

DOI=10.3389/fonc.2023.1297870

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>The prognostic role of Wilms’ tumor 1 (WT1) gene expression at diagnosis in children with B cell precursor acute lymphoblastic leukemia (BCP-ALL) is still controversial.</p></sec><sec><title>Methods</title><p>We detected the WT1 transcript levels of 533 <italic>de novo</italic> pediatric BCP-ALL patients using TaqMan-based real-time quantitative PCR and analyzed their clinical features.</p></sec><sec><title>Results</title><p>The WT1 transcript levels differed among the distinct molecularly defined groups, with the highest levels in the <italic>KMT2A</italic> rearrangements (<italic>KMT2A-r</italic>) group. According to the results of the X-tile software, all patients were divided into two groups: WT1/ABL ≥ 0.24% (group A) and &lt;0.24% (group B). The proportions of patients whose age was ≥10 years old, with immunophenotype of Pro-B, belonging in high-risk group, or with minimal residual disease (MRD) ≥ 0.01% at week 12 were significantly higher in group A than in group B. In the B-other group, WT1 overexpression was an independent risk factor of overall survival (OS) rate (<italic>P</italic> = 0.042), and higher MRD ≥ 0.01% at week 12 was associated with lower OS rate (<italic>P</italic>&lt;0.001) and event-free survival rate (<italic>P</italic>&lt;0.001). Moreover, the subgroup analysis revealed that, in patients with initial WBC&lt;50 × 10<sup>9</sup>/L or MRD&lt;0.1% at day 33 or MRD&lt;0.01% at week 12 or in the standard-risk group, WT1 overexpression led to a poorer outcome in comparison with those with WT1 downexpression (<italic>P</italic>&lt;0.05).</p></sec><sec><title>Discussion</title><p>Therefore, pediatric BCP-ALL with WT1 overexpression had unique clinico-pathological characteristics and poor treatment response. In B-other patients, WT1 overexpression at diagnosis predicted an inferior prognosis. The WT1 gene may serve as a biomarker for monitoring residual disease in the B-other population, especially in children in the standard-risk group.</p></sec>